2025/01/05 更新

写真a

ワカスギ タカユキ
若杉 嵩幸
WAKASUGI Takayuki
所属
医歯学総合病院 魚沼地域医療教育センター 特任助教
職名
特任助教
外部リンク

学位

  • 博士(医学) ( 2019年9月   新潟大学 )

経歴

  • 新潟大学   医歯学総合病院 魚沼地域医療教育センター   特任助教

    2022年4月 - 現在

 

論文

  • Cardiac mitofusin-1 is reduced in non-responding patients with idiopathic dilated cardiomyopathy. 国際誌

    Yung Ting Hsiao, Ippei Shimizu, Takayuki Wakasugi, Yohko Yoshida, Ryutaro Ikegami, Yuka Hayashi, Masayoshi Suda, Goro Katsuumi, Masaaki Nakao, Takuya Ozawa, Daisuke Izumi, Takeshi Kashimura, Kazuyuki Ozaki, Tomoyoshi Soga, Tohru Minamino

    Scientific reports   11 ( 1 )   6722 - 6722   2021年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Prognosis of severe heart failure remains poor. Urgent new therapies are required. Some heart failure patients do not respond to established multidisciplinary treatment and are classified as "non-responders". The outcome is especially poor for non-responders, and underlying mechanisms are largely unknown. Mitofusin-1 (Mfn1), a mitochondrial fusion protein, is significantly reduced in non-responding patients. This study aimed to elucidate the role of Mfn1 in the failing heart. Twenty-two idiopathic dilated cardiomyopathy (IDCM) patients who underwent endomyocardial biopsy of intraventricular septum were included. Of the 22 patients, 8 were non-responders (left ventricular (LV) ejection fraction (LVEF) of < 10% improvement at late phase follow-up). Electron microscopy (EM), quantitative PCR, and immunofluorescence studies were performed to explore the biological processes and molecules involved in failure to respond. Studies in cardiac specific Mfn1 knockout mice (c-Mfn1 KO), and in vitro studies with neonatal rat ventricular myocytes (NRVMs) were also conducted. A significant reduction in mitochondrial size in cardiomyocytes, and Mfn1, was observed in non-responders. A LV pressure overload with thoracic aortic constriction (TAC) c-Mfn1 KO mouse model was generated. Systolic function was reduced in c-Mfn1 KO mice, while mitochondria alteration in TAC c-Mfn1 KO mice increased. In vitro studies in NRVMs indicated negative regulation of Mfn1 by the β-AR/cAMP/PKA/miR-140-5p pathway resulting in significant reduction in mitochondrial respiration of NRVMs. The level of miR140-5p was increased in cardiac tissues of non-responders. Mfn1 is a biomarker of heart failure in non-responders. Therapies targeting mitochondrial dynamics and homeostasis are next generation therapy for non-responding heart failure patients.

    DOI: 10.1038/s41598-021-86209-y

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  • Increased acetylcarnitine does not mediate cardioprotective effects of empagliflozin in a murine heart failure model(和訳中) 査読

    仲尾 政晃, 清水 逸平, 吉田 陽子, 勝海 悟郎, 林 由香, 池上 龍太郎, 須田 将吉, 若杉 嵩幸, 南野 徹

    日本抗加齢医学会総会プログラム・抄録集   19回   211 - 211   2019年6月

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    記述言語:英語   出版者・発行元:(一社)日本抗加齢医学会  

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  • p53 plays a crucial role in endothelial dysfunction associated with hyperglycemia and ischemia. 査読 国際誌

    Masataka Yokoyama, Ippei Shimizu, Ayako Nagasawa, Yohko Yoshida, Goro Katsuumi, Takayuki Wakasugi, Yuka Hayashi, Ryutaro Ikegami, Masayoshi Suda, Yusuke Ota, Sho Okada, Marcus Fruttiger, Yoshio Kobayashi, Masanori Tsuchida, Yoshiaki Kubota, Tohru Minamino

    Journal of molecular and cellular cardiology   129   105 - 117   2019年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    p53 is a guardian of the genome that protects against carcinogenesis. There is accumulating evidence that p53 is activated with aging. Such activation has been reported to contribute to various age-associated pathologies, but its role in vascular dysfunction is largely unknown. The aim of this study was to investigate whether activation of endothelial p53 has a pathological effect in relation to endothelial function. We established endothelial p53 loss-of-function and gain-of-function models by breeding endothelial-cell specific Cre mice with floxed Trp53 or floxed Mdm2/Mdm4 mice, respectively. Then we induced diabetes by injection of streptozotocin. In the diabetic state, endothelial p53 expression was markedly up-regulated and endothelium-dependent vasodilatation was significantly impaired. Impairment of vasodilatation was significantly ameliorated in endothelial p53 knockout (EC-p53 KO) mice, and deletion of endothelial p53 also significantly enhanced the induction of angiogenesis by ischemia. Conversely, activation of endothelial p53 by deleting Mdm2/Mdm4 reduced both endothelium-dependent vasodilatation and ischemia-induced angiogenesis. Introduction of p53 into human endothelial cells up-regulated the expression of phosphatase and tensin homolog (PTEN), thereby reducing phospho-eNOS levels. Consistent with these results, the beneficial impact of endothelial p53 deletion on endothelial function was attenuated in EC-p53 KO mice with an eNOS-deficient background. These results show that endothelial p53 negatively regulates endothelium-dependent vasodilatation and ischemia-induced angiogenesis, suggesting that inhibition of endothelial p53 could be a novel therapeutic target in patients with metabolic disorders.

    DOI: 10.1016/j.yjmcc.2019.02.010

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  • Peptide vaccine for semaphorin3E ameliorates systemic glucose intolerance in mice with dietary obesity. 国際誌

    Yohko Yoshida, Ippei Shimizu, Yuka Hayashi, Ryutaro Ikegami, Masayoshi Suda, Goro Katsuumi, Takayuki Wakasugi, Masaaki Nakao, Hironori Nakagami, Ryuichi Morishita, Tohru Minamino

    Scientific reports   9 ( 1 )   3858 - 3858   2019年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We previously demonstrated that cellular aging signals upregulated a secreted class 3 semaphorin E (Sema3E) and its receptor plexinD1 in the adipose tissue of a murine model of dietary obesity and that Sema3E was a chemoattractant, mediating its biological effects by inducing infiltration of plexinD1-positive inflammatory macrophages into the visceral white adipose tissue. This study was performed to develop a peptide vaccine for Sema3E and test its therapeutic potential in a murine model of dietary obesity. Two antigenic peptides were selected to generate neutralizing antibodies for a vaccine. These peptides were conjugated to keyhole limpet hemocyanin (KLH), and were administered with Freund's adjuvant to obese wild-type male mice. The Sema3E antibody titer was analyzed by ELISA, and the biological effects of the peptides were tested in mice with dietary obesity. Among the two candidate peptides, the Sema3E antibody titer was significantly increased by injection of KLH-conjugated HKEGPEYHWS (Sema3E vaccine). Administration of Sema3E vaccine suppressed the infiltration of plexinD1-positive cells, ameliorated chronic inflammation in visceral white adipose tissue, and improved systemic glucose intolerance in mice with dietary obesity, suggesting that Sema3E vaccine has the potential to become a next generation therapy for obesity and diabetes.

    DOI: 10.1038/s41598-019-40325-y

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  • 新しい老化細胞除去薬と加齢および加齢関連心血管代謝障害(A Novel Senolytic Drug for Aging and Age-related Cardiometabolic Disorders) 査読

    勝海 悟郎, 清水 逸平, 吉田 陽子, 林 由香, 池上 龍太郎, 須田 将吉, 若杉 嵩幸, 仲尾 政晃, 長澤 綾子, 南野 徹

    日本循環器学会学術集会抄録集   83回   PJ126 - 4   2019年3月

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    記述言語:英語   出版者・発行元:(一社)日本循環器学会  

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MISC

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受賞

  • 第250回 日本循環器学会関東甲信越地方会 Clinical Research Award 優秀賞

    2018年12月  

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